3, 5-cyclo-10-hydroxy-19-norandrostan-17-ones and intermediate



United States Patent M 3,087,943 3,5-CYCLO--HYDROXY-19-NORANDROSTAN-17-ONES AND INTERMEDIATE William F. Johns, Morton Grove, Ill., assignor toG. D. Scarle & Co., Chicago, Ill., a corporation of Delaware N0 Drawing.Filed Jan. 2, 1962, Ser. No. 163,847 3 Claims. (Cl. 260-3914) Thisinvention relates to 3,5-cyclo-l0-hydroxy-19- norandrostan-17-ones andintermediates thereto. More particularly, this invention relates to newand useful chemical compounds of the formulas .rl Q0 and especially theintermediate thereto of the formula no-- i in aqueous acetonic potassiumacetate.

The following examples describe in detail compounds illustrative of thepresent invention and methods which have been devised for theirmanufacture. However, the invention is not to be construed as limitedthereby, either in spirit or in scope, since it will be apparent tothose skilled in the art of organic synthesis that many modifications,both of materials and of methods, may be practiced without departingfrom the purpose and intent of this disclosure. Throughout the exampleshereinafter set forth, temperatures are given in degrees centigrade andrelative amounts of materials in parts by weight, except as otherwisenoted. Specific rotations are referred to the D line of sodium.

Example 1 A. 35 tolylsulfonyloxy 19 norandrost-S (10)-en-17- 3,087,943Patented Apr. 30, 1963 0ne.To a solution of approximately 17 parts ofBB-hydrozy-l9-norandrost-5(10)-en-17-one (US. 2,944,067) in 250 parts ofpyridine at 20 is added 14 parts of p-tolylsulfionyl chloride. Theresultant mixture is allowed to stand at room temperatures for 20 hours,whereupon excess aqueous potassium bicarbonate is introduced; and themixture thus obtained is extracted with benzene. The benzene extract isconsecutively washed with water, excess aqueous hydrochloric acid,water, and aqueous potassium bicarbonate. It is then dried overmagnesium sulliate and freed of solvent by vacuum distillation. Theresidue, crystallized from methanol and then from a mixture of ether andpetroleum ether, affords3,8-tolylsulfonyloxy-l9-norandrost-5(10)-en-17-one melting atapproximately 133-134 and further characterized by a specific rotationof +238.

B. 30,5a cyclo 1018 hydroxy 19 norana'rosmn-U- one.--A mixture of 37parts of 3fi-tolylsulfonyloxy-l9- norandnost-5(10)-en-17-one dissolvedin 1120 parts of acetone and 144 parts of potassium acetate dissolved in1000 parts of water is maintained with agitation at 25 fior 6 hours,then heated at the boiling point under reflux with agitation for 20hours. The acetone is thereupon distilled off, and the residue isextracted with benzene. The benzene extract is stripped of solvent bydistillation; and the residue is chromatographed on silica gel, usingbenzene and ethyl acetate in increasing amounts of the latter asdeveloping solvent. From eluates comprising 5% ethyl acetate in benzene,on distillation of solvent, two products are obtained. The less polarproduct is 3a,Sa-cyclo-l0,8-hydroxy-l9-norandrostan-l7-one which,recrystallized from a mixture of acetone and petroleum ether, affords3a,5u-cyclo-1Op-hydrQXy-I9-norandrostan- 17-one melting at 193-195 andfurther characterized by A. 3ozhydroxy-IQ-norandrost-S(10)-en-17-0ne.The more polar of the two productsobtained by chromatography of the reaction product described in theforegoing Example 113 is 3u-hydroxy-19-norandrost-5(l0)-en-l7- onemelting at 137-139 and having a specific rotation of +206".

B. 30: tolylsulfonyloxy 19 norandrost-5(10)-en-17- one.-'I o a solutionof 8 parts of 3a-hydroxy-l9-norarndrost-5(10)-en-17-one in 300 parts ofpyridine at 5 is added 10 parts of p-tolylsulfionyl chloride. Theresultant solution is allowed to stand at room temperatures tor 20hours, then diluted with excess aqueous potassium biscarbonate andthereupon extracted with benzene. The benzene extract is consecutivelywashed with water, excess aqueous hydrochloric acid, water, and aqueouspotassium bicarbonate, tollowing which it is dried over anhydrousmagnesium sulfate and stripped of solvent by vacuum distillation. Theresidue is chnomatographed on silica gel, using benzene and ethylacetate in increasing amounts of the latter as developing solvent. Froman eluate comprising 2% ethyl acetate in benzene, on distillation ofsolvent, is obtained 3attolylsulfonyloxyd9-nonandrost- 5(10)-en-17-onewhich, recrystallized from a mixture of 3 4 acetone and petroleum ether,melts at approximately What is claimed is: 138-l39 and is furthercharacterized by a specific rotal. A compound selected from the groupconsisting of tion of +148 a compound having the formula C. 35,55 cyclo10a hydroxy 19 nrandr0stan-17- 0ne.-A solution of 2 parts of30L-llO1YlSl1lfOIlY1OXY-19- norandrost-5(10)-en-17-one in 80 parts ofacetone and a solution of parts of potassium acetate in 80 parts ofwater are mixed at room temperature and maintained OH thereat withagitation for 6 hours, then heated at the boil- HBO ing point underreflux with agitation for an additional 24 10 hours. The resultantsolution is cooled and extracted with benzene. The benzene extnact isstripped of solvent V by distillation; and the residue ischromatographed on andlawmpound having the f l silica gel, using benzeneand ethyl acetate in increasing amounts of the latter as developingsolvent. From an H3O elu-ate comprising 10% ethyl acetate in benzene,[on disti1- lation of solvent and recrystallization of the residue frompetroleum ether, is obtained 3,6,513-cyclo-10a hydroXy-19- OHnorandrost-an-l7-one melting at 173-176" and with a /\l specificrotation of +136. The product has the formula 20 l 2. 311,5a-cyclo-10/S-hydroxy-19-norandrostan-17-one. 3.33,5,8-cycl0-10a-hydrQXy-l9-a1orandr0stan-l7-one.

- References Cited in the file of this patent UNITED STATES PATENTS2,944,068 Johns July 5, 1960

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF A COMPOUND HAVINGTHE FORMULA